The proposed research will continue our studies into the mechanism(s) of glucocorticoid-induced increase in intraocular pressure. We have recently demonstrated the presence of a glucocorticoid receptor in iris-ciliary body and adjacent corneoscleral tissue of the rabbit by both biochemical and radioautographic techniques. We have subsequently showed the nuclear translocation of this glucocorticoid receptor following an injection of physiologic doses of active glucocorticoids indicating the presence of specific target cells within this tissue. We plan to identify in the human outflow region specific glucocorticoid target cells. Glucocorticoid-induced gene products will be identified in these target tissues utilizing primary and secondary cell lines developed in tissue culture. The focus of this aspect of the study will be to determine differences in steroid gene expression in primary open angle glaucoma (POAG) versus non-POAG derived tissues. We speculate that specific gene products induced by glucocorticoids, in one or more of these target tissues may play a physiologic role in the regulation of intraocular pressure and that one or more defects in the regulation of these products may be found in ocular tissues of steroid sensitive patients (POAG) resulting in an increased resistance to outflow. Our studies involving the metabolic fate of glucocorticoids in the tissue culture cell lines and the effect of enzyme inducing agents on this metabolism will be continued.